vaccine therapy and sargramostim compared with placebo and sargramostim following rituximab in treating patients with non-hodgkin's lymphoma

Conditions: Lymphoma

Summary: rationale: monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. vaccines made from a person's cancer cells may make the body build an immune response to kill cancer cells. colony-stimulating factors such as gm-csf increase the number of immune cells found in bone marrow and peripheral blood. it is not yet known whether combining rituximab and gm-csf with vaccine therapy may cause a stronger immune response and kill more cancer cells. purpose: this randomized phase iii trial is studying giving rituximab and gm-csf together with vaccine therapy and comparing it to giving rituximab and gm-csf alone in treating patients with newly diagnosed, relapsed, or refractory b-cell non-hodgkin's lymphoma.

objectives: primary * compare time to disease progression in patients with grade 1, 2, or 3 follicular b-cell non-hodgkin's lymphoma who respond (i.e., complete or partial response, or stable disease) to treatment with rituximab and are then treated with sargramostim (gm-csf) with vs without autologous immunoglobulin idiotype-klh conjugate vaccine. secondary * compare response rate improvement in patients treated with these regimens. * compare overall complete response rate in patients treated with these regimens. * compare duration of response in patients treated with these regimens. * determine the safety of these regimens in these patients. outline: this is a randomized, double-blind, placebo-controlled, multicenter study. patients are stratified according to prior treatment (yes vs no) and response to rituximab during study (complete response \[cr\] or partial response \[pr\] vs stable disease \[sd\]). all patients receive rituximab iv once weekly for 4 weeks. five weeks after the last dose of rituximab, patients are assessed for response. patients with progressive disease are removed from the study and do not undergo randomization. patients with a cr, pr, or sd are randomized to 1 of 2 treatment arms. * arm i: patients receive autologous immunoglobulin idiotype-klh conjugate vaccine subcutaneously (sc) on day 1. patients also receive sargramostim (gm-csf) sc on days 1-4. * arm ii: patients receive placebo sc on day 1. patients also receive gm-csf sc on days 1-4. in both arms, treatment repeats monthly for 6 months in the absence of unacceptable toxicity or clinically significant progressive disease. after the first 6 months, patients with a cr, pr, or sd may continue to receive treatment (per treatment arm as above) every 2 months for 1 year (total of 6 doses) and then every 3 months thereafter in the absence of disease progression. patients are followed every 3 months for 2 years and then every 6 months until disease progression. projected accrual: a total of 342 evaluable patients (171 per treatment arm) will be accrued for this study within 18 months.

Eligibility criteria:
disease characteristics: * histologically confirmed follicular b-cell non-hodgkin's lymphoma (nhl) * grade 1, 2, or 3 * meets 1 of the following criteria for treatment with rituximab: * treatment naïve * relapsed or refractory disease after prior chemotherapy * relapsed after a prior documented response (i.e., complete or partial response) to rituximab of at least 6 months duration * tumor accessible for biopsy or existing biopsy material (taken within the past 6 months) suitable for vaccine preparation * measurable or evaluable disease after tumor tissue procurement for vaccine production * no more than 2 prior treatment regimens for nhl * single regimens include any of the following: * maintenance rituximab * rituximab administered once weekly for 8 courses * cyclophosphamide, doxorubicin, vincristine, and prednisone (chop) plus rituximab\* note: \*chop followed by rituximab at time of relapse is considered 2 treatment regimens * no history of cns lymphoma or meningeal lymphomatosis patient characteristics: age * 18 and over performance status * ecog 0-1 life expectancy * not specified hematopoietic * absolute granulocyte count ≥ 1,500/mm\^3 * platelet count ≥ 75,000/mm\^3 (unless related to bone marrow involvement by lymphoma) * hemoglobin ≥ 10g/dl hepatic * not specified renal * not specified cardiovascular * no congestive heart failure pulmonary * no compromised pulmonary function immunologic * hiv negative * no prior allergic response to gm-csf * no active bacterial, viral, or fungal infection other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no psychiatric disorder that would preclude study participation * no other malignancy within the past 2 years except nonmelanoma skin cancer or carcinoma in situ of the cervix * no other serious nonmalignant disease that would preclude study participation prior concurrent therapy: biologic therapy * see disease characteristics * see chemotherapy * at least 4 weeks since prior immunotherapy * no prior radiolabeled anti-lymphoma antibody (e.g., iodine i 131 tositumomab or ibritumomab tiuxetan) * no prior autologous or allogeneic stem cell transplantation * no prior lymphoma-specific idiotype immunotherapy (e.g., id vaccine) * no prior investigational vaccine or immunotherapeutic containing keyhole limpet hemocyanin (klh) chemotherapy * see disease characteristics * at least 4 weeks since prior chemotherapy * more than 9 months since prior fludarabine * more than 2 years since prior chemotherapy/rituximab combination therapy (e.g., chop/rituximab or cyclophosphamide, vincristine, and prednisone \[cvp\]/rituximab) * no more than 6 total prior treatment courses with fludarabine endocrine therapy * no concurrent steroids for allergic reaction to sargramostim (gm-csf) radiotherapy * see biologic therapy * at least 4 weeks since prior radiotherapy surgery * not specified other * at least 4 weeks since prior experimental therapy * no concurrent systemic immunosuppressive therapy * no other concurrent anti-lymphoma therapy

Keywords: contiguous stage ii grade 1 follicular lymphoma contiguous stage ii grade 2 follicular lymphoma contiguous stage ii grade 3 follicular lymphoma noncontiguous stage ii grade 1 follicular lymphoma noncontiguous stage ii grade 2 follicular lymphoma noncontiguous stage ii grade 3 follicular lymphoma stage i grade 1 follicular lymphoma stage i grade 2 follicular lymphoma stage i grade 3 follicular lymphoma stage iii grade 1 follicular lymphoma stage iii grade 2 follicular lymphoma stage iii grade 3 follicular lymphoma stage iv grade 1 follicular lymphoma stage iv grade 2 follicular lymphoma stage iv grade 3 follicular lymphoma recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma